Antimycobacterials Flashcards
What is the MOA of Isoniazid?
Inhibits biosynthesis of mycolic acid (component of cell wall)
Requires KatG for activation
What are the uses of Isoniazid?
Mycobacterium tuberculosis (both active and latent)
Must be used with RIF, EMB, and PZA in active TB
Can be used alone in latent TB
What are toxicities of Isoniazid?
- Hepatotoxicity (fast acetylators)
- Peripheral neuritis (slow acetylators)
- Hemolysis (G6PD deficiency)
- Lupus like syndrome (HIP drug)
- Seizures, insomnia
What is the DOC for Mycobacterium tuberculosis?
Isoniazid
What is the MOA for Rifampin?
Inhibits DNA dependent RNA polymerase
What are the uses of Rifampin?
- Mycobacterium tuberculosis (both active and latent)
- Mycobacterium avium complex (MAC)
- Mycobacterium leprae
(Must be used with INH, EMB, and PZA in active TB)
What are toxicities of Rifampin?
- Hepatic enzyme induction (cytochrome P450s)
- Decreased effectiveness of birth control
- Orange color to secretions
- GI disturbances
- Hypersensitivity/allergy
What population should Rifampin be avoided in?
HIV-treated individuals
What is the DOC for Mycobacterium leprae?
Rifampin + Dapsone
What is the MOA for Ethambutol?
Inhibits arabinosyl transferase involved in the synthesis of arabinogalactan (in cell wall)
What are the uses of Ethambutol?
- Mycobacterium tuberculosis (TB)
- Mycobacterium avium complex (MAC)
What combination of drugs can be used to treat Mycobacterium avium complex (MAC)?
Ethambutol + clarithromycin + rifabutin/rifampin/cipro
OR
Ethambutol + azithromycin + rifabutin/rifampin/cipro
What are major toxicities of Ethambutol
- Decreased visual acuity and loss of green-red perception
- Renal insufficiency (give smaller dose)
What population should Ethambutol be avoided in?
Children under 13 years of age due to adverse effects on vision
When is Pyrazinamide active and when does it have its greatest activity?
Active in acidic pH
Has greatest activity against dormant organisms
What are the uses of Pyrazinamide?
Mycobacterium tuberculosis (optimal within macrophages due to activity at acidic pH)
(Must be given with INH, RIF, and EMB in active TB)
What are toxicities of Pyrazinamide?
- Hepatic dysfunction
- Hyperuricemia (lead to gout flares)
- GI, myalgia, photosensitivity, porphyria
What is the MOA of Rifabutin?
Inhibits DNA dependent RNA polymerase
What are the uses of Rifabutin?
- Active Mycobacterium tuberculosis with co-infection of HIV
- Mycobacterium avium complex (MAC)
What is the DOC for Mycobacterium tuberculosis WITH co-infection of HIV?
Rifabutin
What is an advantage of Rifabutin over Rifampin?
Rifabutin is a less potent inducer of P450 enzymes
What is the MOA of Rifapentine?
Inhibits DNA dependent RNA polymerase
What are the uses of Rifapentine?
Latent Mycobacertium tuberculosis (including HIV+ patients)
What is the DOC for LATENT Mycobacertium tuberculosis (including HIV+)?
Isoniazid + Rifapentine
What is the MOA for Dapsone?
PABA antagonist
What are the uses of Dapsone?
Mycobacterium leprae (+ RIF)
What are the toxicities of Dapsone?
- Nasal obstruction (improves in 3-6 months)
- Dose related hemolysis
- Agranulocytosis
- Peripheral neuritis
What are the uses of Thalidomide?
Moderate to severe ENL
What are toxicities of Thalidomide?
Teratogenic!
What is the DOC for moderate to severe ENL?
Thalidomide
What drugs are used for Latent TB?
- INH monotherapy
- Rifampin monotherapy
- Rifapentine + INH
